Motor and memory testing of long-lived pregnancy-associated plasma protein--a knock-out mice.

Unlabelled: Mice deficient in pregnancy-associated plasma protein-A (PAPP-A), an IGF binding protein protease, have been shown to be resistant to experimentally induced atherosclerosis and diabetic nephropathy, and, in the laboratory environment, live 30-40% longer than wild-type littermates in association with delayed incidence and occurrence of age-related neoplasms and degenerative diseases.

Objective: PAPP-A is highly expressed in the cerebellum and hippocampus of the mouse brain. Therefore, the studies presented here were aimed at determining motor behavior, learning and retention in PAPP-A knock-out (KO) mice compared to wild-type (WT) littermates with age.

Insulin-like growth factor (IGF)-I and IGF-II contribute differentially to the phenotype of pregnancy associated plasma protein-A knock-out mice.

Context: Insulin-like growth factor (IGF) signaling is essential for achieving optimal body size during fetal development, peak bone mass during puberty, and maximal fecundity in the reproductive period. IGF-II is considered the main fetal IGF, whereas IGF-I is more important postnatally. Pregnancy-associated plasma protein-A (PAPP-A) enhances local IGF signaling through cleavage of inhibitory IGF binding proteins.

Pregnancy-associated plasma protein-A2 (PAPP-A2): tissue expression and biological consequences of gene knockout in mice.

Pregnancy-associated plasma protein-A2 (PAPP-A2) is a novel homolog of PAPP-A in the metzincin superfamily. However, compared with the accumulating data on PAPP-A, very little is known about PAPP-A2. In this study, we determined the tissue expression pattern of PAPP-A2 mRNA in wild-type (WT) mice and characterized the phenotype of mice with global PAPP-A2 deficiency.

Longevity is not influenced by prenatal programming of body size.

Insulin-like growth factor (IGF) signaling is essential for achieving optimal body size during fetal development, whereas, in the adult, IGFs are associated with aging and age-related diseases. However, it is unclear as to what extent lifespan is influenced by events that occur during development. Here, we provide direct evidence that the exceptional longevity of mice with altered IGF signaling is not linked to prenatal programming of body size.